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Exciting news ElZorro. Here's another article from last Friday about this vaccine research, with a little more detail about the vaccine trial. There were 128 participants in Phase 1 which monitored their progress for 48 weeks, and there's 160 people in phase 2 which is not yet completed but they decided to publish the good news anyway. Is this group part of CHAVI? Does anyone have more information?

Italian AIDS Virus vaccine "working" 12/11/2010- A ground-breaking Italian AIDS vaccine appears to be working, researchers said Friday. "We have seen the vaccine reach parts where drugs cannot go," said lead researcher Barabara Ensoli of the Higher Health Institute (ISS). It was "thrilling" to see the results, which have been published in the Plos One journal, she said.

"The vaccine seems to bring the immune system back into kilter". Testing is currently at the second stage and should be completed "with another 160 patients," Ensoli said. "Even so, we decided to publish now because we have achieved statistically significant results very quickly," said the researcher, who has been working on the vaccine for 10 years.

Ensoli noted that 48 weeks after the vaccine was given to the volunteers, "their parameters are still improving and it appears we have managed to stop the damage". ISS Chair Enrico Garaci said the results "corroborate our efforts" and "confirm our model of research, from the lab bench to the patient's bed". He made an appeal to private and public bodies for funding to complete the current round of tests.

The second stage of testing began in late 2008 in ten centres across Italy with 128 HIV-positive people between the ages of 18 and 55, both men and women. In 2006 Ensoli ended the first phase of research and reported that her AIDS vaccine had passed its initial tests with flying colours. She said all the Italian volunteers had shown a ''100% response to the vaccine by producing specific antibodies''.

Ensoli's vaccine is considered ground-breaking because it adopts a new approach to fighting HIV, the virus that causes AIDS. Traditional vaccines seek to bolster the immune system, the aim being to boost the body's ability to fight off the disease. This approach, however, has been relatively unsuccessful against HIV, a virus good at mutating and reviving itself. Ensoli's 'tat-protein' vaccine, on the other hand, attempts to block the spread of the infection and prevent the reproduction of infected cells.

Ensoli believes the HIV virus needs tat-proteins to be able to take root and spread. By targeting tat-proteins her treatment might be effective against all strains of HIV. Results from studies of the vaccine on laboratory animals have shown the treatment could be a vital step forward in the fight against AIDS.

The vaccine - described by eminent oncologist and former health minister Umberto Veronesi as ''intelligent'' - received the green light for human testing in 2003. Ensoli's technique is not without its critics, however. In August 2007 the American magazine Science reported that Ensoli had filed a suit against prominent immunologist Ferdinando Aiuti accusing him of slander and seeking to tarnish her reputation.

Aiuti, Science wrote, had repeatedly cited ''critical errors'' in the first experimental stages of Ensoli's vaccine. Aiuti said he was ''surprised'' about the suit, adding that he had ''nothing personal'' against Ensoli and that he had not changed his opinion on her experimental vaccine.

Here is some of the science behind the vaccine research. Includes a special mention for LTS:

The interim results of the randomized phase II trial, conducted in 87 HAART-treated patients, 48 weeks after vaccination indicate that not only is the Tat vaccine safe and capable of inducing specific antibody and cellular immune responses, but it also has a key and novel role in reducing immune system alterations observed in HIV infection, which usually persist even under successful HAART. Further, those patients who are the most immunocompromised may benefit the most from Tat vaccination.

Thanks for the good news this afternoon.There is always hope somewhere if we choose to look.

Cheers,Hoover and Dr T.

agreed!

From what I can determine from researching Dr. Ensoli and this Tat vaccine, she and her team have been working on the same hypothesis since pre-1994. I personally find it pretty exciting that they continue to pursue the same hypothesis and they have yet to be disappointed. Granted, this appears to be an adjunct to HAART that seems to provide great benefits to compromised immune systems, but I don't think it is too far a stretch to hope that it could continue on to supplant HAART once the science is fully developed.

Here's to hoping they continue to have more successes and (importantly) can raise the funds that they need to "getter done"

Here's another article about the vaccine trial, with more detailed statistics about how it caused significant increases in interlukin 2 (IL2) as well as IL4, and interferon-gamma, improved CD4 and B cell counts. It also reduced CD8 counts, which is evidence that it reduced chronic immune activation and inflamation that people on HAART continue to experience.

A therapeutic HIV vaccine appears to reverse some of the immune dysfunction caused by the virus, researchers reported.

According to preliminary data from a randomized phase II trial, a vaccine against the HIV protein Tat was both safe and immunogenic, according to Barbara Ensoli, MD, PhD, of the National AIDS Center of the Istituto Superiore di Sanità in Rome, and colleagues.

But in patients with fully suppressed HIV replication, the vaccine also appeared to improve a range of markers of immune function, Ensoli and colleagues reported online in PLoS One.

Even when highly active anti-retroviral therapy (HAART) slows HIV replication, there is often enough growth to cause continued immune activation in patients, Ensoli and colleagues noted, and immune homeostasis is impaired.

The Tat protein is essential for HIV replication, so Ensoli and colleagues are testing several doses and vaccination schedules of a recombinant protein in a phase II randomized trial, designed to determine immunogenicity and safety.

But a secondary goal is to see what effect the vaccine has on immune parameters, including such things as the number of B cells, CD4-positive T cells, and CD8-positive T cells.

For this analysis -- described as "ad hoc and exploratory" -- Ensoli and colleagues analyzed results from 87 volunteers and compared them with patients taking part in a separate, prospective observational trial that is examining the effect of naturally-occurring Tat immunity.

The 87 volunteers in the trial had no antibodies to Tat, but had undetectable HIV on a range of HAART regimens. They were given either 7.5 or 30 micrograms intradermally, either three or five times.

Overall, Ensoli and her colleagues found, 79% of the volunteers responded to the vaccine by producing antibodies to Tat.

Although 59% of the volunteers had at least one adverse event, they were mostly the usual side effects associated with HIV infection, the researchers said. Of those that were linked to the Tat vaccine most were local, related to the injection, and mild.

The researchers reported seven serious adverse events, but only one -- a severe case of disarthria and paresthesia -- was regarded as possibly related to the drug. It resolved after the vaccine was stopped.

The researchers also found that responders had:

• Significant increases in interleukin-2, interferon-gamma, and interleukin-4, as well as Tat-specific CD4 and CD8 T cells

• Improvements in the in vitro viability of peripheral blood mononuclear cells, which is lessened in HIV infection, that continued to increase for up to 48 weeks and were significant at that point at P<0.0001

• Increases in the number of CD4 T cells, ranging on average from 48 to 69 cells/mL of blood, depending on dose

• Increases in the number of B cells that ranged on average from 25 to 66 cells/mL of blood

• An increased proportion of CD4 T cells and B cells, but a decrease in the proportion of CD8 T cells and natural killer cells -- a marker of immune activation

The responses, in general, were better with the larger dose, the researchers reported.

The results, Ensoli said in a statement, "suggest that therapeutic vaccination with the Tat vaccine, combined with HAART, can significantly improve the recovery of the immune system in patients with HIV."

The study was supported by the Italian health ministry.The researchers said they had no disclosures.

Finally some news from Italy! We've been waiting to hear from this anti-Tat vaccine candidate for years now. At least it's some good news, although I am just a tad disssapointed at Ensoli's statement:

"The results suggest that therapeutic vaccination with the Tat vaccine, combined with HAART, can significantly improve the recovery of the immune system in patients with HIV."

Perhaps they are being conservative on the therapeutic potential of the vaccine, but I was hoping more of "this vaccine could make haart unecessary". Time will tell I guess. Just hope it doesn't take another three years before we hear from them again.

But still, excellent news! Could it be the light at the end of the tunnel? Oh, what a glorious day it will be....

Logged

"Hope is my philosophy Just needs days in which to beLove of Life means hope for meBorn on a New Day" - John David

A phase I clinical trial consists in the experimental administration of a drug to humans. It is conducted on a very small number of volunteers. Patients can be healthy or affected by the disease which the vaccine aims to prevent or cure. The major goal of a phase I study is to evaluate vaccine tolerability and safety on humans.

8. What is a Phase II trial?

Once Phase I trial has shown the experimental drug is safe and well tolerated, it can move to Phase II. The number of participants is usually low, even though higher than in Phase I. The major aim of Phase II trial is to assess the efficacy of the drug at inducing a specific immune response. Nonetheless, safety and tolerability evaluation is not disregarded. The results of this Phase are aimed to demonstrate the drug immunogenicity and to define doses and administration protocols. Phase II trials can be conducted either to define new indications and doses for commercialized drugs, or to test treatment combinations aimed at reaching a synergistic effect that can improve treatment efficacy. This phase usually lasts at least 2 years. - edited to add: elsewhere on the site they indicate that this Phase II will last 4 years.

9. What is a Phase III trial?

Once Phase I and II trials have given positive results, the study can move to Phase III. In this phase, the drug is administered to a higher number of patients (thousands), in the doses and means that have been previously defined. Given the higher number of volunteers, the researchers can collect more information than those received in the previous phases, especially concerning adverse events and rare diseases. This phase is aimed at proving both preventive and therapeutic advantages of the drug. A Phase III trial can last about 2-4 years and, in case of positive results, the treatment can be registered and widely distributed.

The data being discussed right now is 48 weeks into Phase II. I gather from the reading that we're looking at another 3+ years for Phase II to complete. Then (assuming continued success) on to Phase III after whatever duration it takes to gather approval etc. Doing the match conservatively, if they continue to enjoy the same successes they experienced for the past 15+ years, the "end" could be anywhere from 8-10 years from now.

El z, could you go into a little more detail about how you've concluded that it'll be over in 8-10 years? From your explanation of the clinical trial process and what I can infer about this new approach, it looks more like a useful anti-inflammatory drug may be available in about three years.

Assuming (hoping?) they continue to be successful, they would have to complete Phase III trials that they indicate could be 2-4 years. Of course, there would likely be delays between the two trials and then (again assuming success), they would have to move through the approval and production stages. Using the high numbers, we arrive at 7 years to just complete the trials. How long after, that? I'm not really the one to ask. Maybe a LTS who has watched HAART evolve can chime in.

I'd bet, though, that if they are successful, there will be a worldwide push to help to fast track anything after Phase III. Let's hope that their recent results gain them some money raising attention.

On a lighter side, I'm not sure why, but I keep having flashes of seeing "Dr Gallo" jetting off to Italy to bust up the party and take credit I recently watched "And The Band Played On" again...I really don't care for that man very much.

I'm sorry everyone, I don't mean to beat a dead horse, but am I correct that this appears to be just another treatment, and not an actual cure?

WTF

Take a look at the FAQ on the site that V posted. They answer a lot of questions similar to this one. For now, it's "wait and see" but very promising. The great news is the impact it may have on a damaged immune system.

15. Is the Tat vaccine both preventive and therapeutic?

This vaccine could reduce viral replication and, thus, it can be used both as a preventive vaccine that blocks the initial cycles of virus replication, preventing HIV spread in the organism, and as a therapeutic one, because the reduction of viral replication, similarly to anti-retroviral treatments, can slow or block disease progression in HIV positive individuals. To verify whether this vaccine is an acceptable and efficient treatment against HIV infection may take many years.

49. Can the Tat vaccine replace the antiretroviral therapy?

This is not known at present. Additional studies are needed to give an answer to this question. In this phase II study the Tat vaccine has been tested on HIV-infected HAART-treated individuals with suppressed plasma viremia. Therefore, the subjects immunized with the vaccine continued to take the antiretroviral drugs. The synergistic effect of vaccination and antiretroviral treatment is the subject of the scientific publication in PLoS ONE.

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

I think so too, but I also suspect it will emerge that some strains of hiv will respond better than others, just like with hep C. Some hcv genotypes are notoriously difficult to treat.

Since the thread was brought back up.... I've thought about this, too, and what effects it will have if some HIV strains are able to be cured or functionally cured and others have strains that can't be or not that well. I think it will cause a huge divide between the poz community. I hope for a cure in any form, but I hope it works for everyone. However, I do think it could turn out like treatments for Hep C. But, I really don't think we have to worry about this in the near future....just one of those things to think about at 1am.

Since the thread was brought back up.... I've thought about this, too, and what effects it will have if some HIV strains are able to be cured or functionally cured and others have strains that can't be or not that well. I think it will cause a huge divide between the poz community. I hope for a cure in any form, but I hope it works for everyone. However, I do think it could turn out like treatments for Hep C. But, I really don't think we have to worry about this in the near future....just one of those things to think about at 1am.

It hasn't caused a "huge divide" in the hep C community, so why would it cause one in the hiv community? Sometimes I think you just like looking for drama where none exists.

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts